Title:
弱酸に不安定であるアミノ保護基を使用するPNAの合成
Document Type and Number:
Japanese Patent JP4098837
Kind Code:
B2
Abstract:
A process is claimed for preparing peptide nucleic acid (PNA) oligomers of formula (I) B-X = a gp. of formula (i)-(viii): f = 1-4; g = 0-3; Ro = H, 1-18C alkanoyl, 2-19C alkoxycarbonyl, 3-8C cycloalkanoyl (sic), 7-15C aroyl, 3-13C heteroaroyl or a gp. which enhances intracellular uptake of the oligomer or interacts with a target nucleic acid during hybridisation; A and Q = amino acid residues; k and m = 0-10; B = a natural or non-natural nucleotide base, opt. in prodrug form, or a base substitute; Qo = OH, NH2 or NHR"; R" = 1-18C alkyl, 2-18C aminoalkyl or 2-18C hydroxyalkyl; n = 1-50. The process comprises: (a) opt. coupling amino acids (Q<1>) to a support of formula L-(Polymer) by solid-phase synthesis, where L = a linking gp. contg. Qo in latent form and Q<1> = Q with optional side-chain protecting; (b) opt. removing the protecting gp. PG (sic) with a suitable reagent; (c) repeating steps (a) and (b) m-1 times to give (Q<1>)m-L-(Polymer); (d) coupling a cpd. of formula (II) to L-(Polymer) or (Q<1>)m-L-(Polymer): PG-X(B<1>)-OH (II) where PG is a weak-acid-labile protecting gp. and B<1> is B with opt. protected exocyclic amino or OH gps.; (e) removing PG; (f) repeating steps (d) and (e) n-1 times; (g) opt. coupling amino acids (A<1>) to the prod. by solid-phase synthesis, where A<1>=A with optional side-chain protection; (h) removing the protecting gp. PG (sic) with a suitable reagent; (i) repeating steps (g) and (h) k-1 times; (j) introducing Ro if Ro is other than H; and (k) cleaving the PNA oligomer from the prod. of formula (III) and simultaneously or subsequently deprotecting B<1>, A<1> and Q<1>: Ro-(A<1>)k-(X(B<1>))n-(Q<1>)m-L-(Polymer) (III).
Inventors:
Gerhard Breipol
Eugen Uhlmann
Eugen Uhlmann
Application Number:
JP5464295A
Publication Date:
June 11, 2008
Filing Date:
March 14, 1995
Export Citation:
Assignee:
Hoechst Gesellschaft Mito Beschlenktel Haftung
International Classes:
C07K1/04; C07K1/10; C07D239/46; C07D239/54; C07D473/18; C07D473/34; C07K1/06; C07K14/00; C08G69/06; C08G69/10
Domestic Patent References:
| JP7258222A | ||||
| JP7502509A | ||||
| JP7291909A |
Foreign References:
| WO1992020703A1 |
Other References:
Peptide Research,1992年,5(4),245-6
J Am Chem Soc,1992年,114,9677-8
J Org Chem,1994年 9月,59,5767-73
J Am Chem Soc,1992年,114,9677-8
J Org Chem,1994年 9月,59,5767-73
Attorney, Agent or Firm:
Chika Takagi
Tatsuo Sato
Kosuke Nishimura
Tatsuo Sato
Kosuke Nishimura